Molecular Genetics in IgA Nephropathy

Galla, John H.

doi:10.1159/000045969

Cited by 27 publications

(15 citation statements)

References 40 publications

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“…Despite the presence of genes coding for renin, AngII, and ACE in cultured mesangial cells and in mesangial cells in kidney tissues from patients with IgAN (35), information regarding the RAS in IgAN remains scarce and is mainly limited to ACE-related polymorphism. To date, data on the pathogenetic role of different genotypes in IgAN remain divergent and inconclusive (36).…”

Section: Discussionmentioning

confidence: 99%

Polymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System

Lai¹,

Tang²,

Guh

et al. 2003

Journal of the American Society of Nephrology

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Abstract. The effects of polymeric IgA1 (pIgA1) and monomeric IgA1 (mIgA1) from patients with IgA nephropathy (IgAN) on the renin-angiotensin system (RAS) and TGF-␤ synthesis were examined in cultured human mesangial cells (HMC). Both pIgA1 and mIgA1 induced renin gene expression in HMC, in a dose-dependent manner. Similar findings were observed for TGF-␤ gene and protein expression. The values measured in HMC incubated with pIgA1 were significantly higher than those in HMC incubated with equivalent amounts of mIgA1.

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Section: Discussionmentioning

confidence: 99%

Polymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System

Lai¹,

Tang²,

Guh

et al. 2003

Journal of the American Society of Nephrology

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“…4,5 In addition to these prognostic risk factors, several genetic backgrounds have been proposed to be associated with a susceptibility to ESRD in patients with IgAN. 6,7 Recently, interactions among multiple genetic variants of complex traits, including blood pressure regulation as well as the prognosis of kidney disease, have been suggested.…”

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confidence: 99%

Interaction Between ACE and ADD1 Gene Polymorphisms in the Progression of IgA Nephropathy in Japanese Patients

et al. 2003

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Abstract-An interaction effect between the angiotensin-converting enzyme insertion/deletion (ACE I/D) and ␣-adducin (ADD1) Gly460Trp polymorphisms (G460W) on blood pressure regulation has recently been suggested, although its significance in the prognosis of renal function in IgA nephropathy (IgAN) has not been fully investigated. Therefore, we evaluated the clinical manifestations and renal prognosis in 276 Japanese patients with histologically proven IgAN with respect to their ACE I/D and ADD1 G460W polymorphisms. The prognosis of renal function was analyzed by Kaplan-Meier survival curves and multivariate Cox proportional-hazards regression models. Baseline data, including blood pressures, proteinuria, renal function, and incidence of hypertension, were similar for the different genotypes of ACE and ADD1. The individual genotypes taken alone were not associated with the progression of renal dysfunction. However, renal survival of patients with the 460WW polymorphism of ADD1 was significantly worse within the group with the II genotype of ACE (Kaplan-Meier, log rank test; 2 ϭ6.062, Pϭ0.0138) but not for those with other ACE genotypes. In the Cox proportional-hazards regression model with adjustment for clinical risk factors, including hypertension, proteinuria, and no administration of an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the 460WW variant of ADD1 was a highly significant and independent risk factor only for patients with the ACE II genotype, with a hazard ratio of 3.65 (Pϭ0.0016), but not for those with other ACE genotypes (hazard ratioϭ0.65, Pϭ0.2902). These findings suggest an interaction between ACE and ADD1 polymorphisms not only on blood pressure regulation but also on the progression of renal dysfunction in patients with IgAN.

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“…The actuarial renal survival in Japanese patients with IgAN at 10 years and 20 years is assumed to be 85% and 61%, respectively, from the time when the first renal abnormalities are detected (Koyama et al, 1997). Familial clustering of IgAN and interindividual differences in the clinical course suggests that genetic factors may contribute to both the development and progression of this disease (Galla, 2001;Hsu et al, 2000). It has been well documented that impairment of renal function, severe proteinuria, and arterial hypertension at the time of diagnosis are the strongest and most reliable clinical predictors of progression to ESRD (D'Amico, 2000;Koyama et al, 1997).…”

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confidence: 99%

Genetic Polymorphism of NPHS1 Modifies the Clinical Manifestations of Ig A Nephropathy

Narita

Goto

Saito

et al. 2003

Laboratory Investigation

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SUMMARY:Nephrin, the molecule responsible for congenital nephrotic syndrome of Finnish type, is crucial in maintaining the glomerular filtration barrier. Recently, its complete gene structure and common gene polymorphisms in its exons have been reported, although the functional and clinical significance of these polymorphisms has not yet been elucidated. We investigated a possible association of the NPHS1 polymorphisms with the development of Ig A nephropathy (IgAN), as well as the clinical and histologic manifestations in IgAN. A total of 464 Japanese subjects, including 267 patients with histologically proven IgAN and 197 healthy controls with normal urinalysis, were genotyped for the NPHS1 G349A, G2289A, and T3315C polymorphisms. The frequencies of the genotypes, alleles, and estimated haplotypes of NPHS1 polymorphisms were no different between patients with IgAN and the controls. Within the IgAN group, patients carrying at least one G allele of G349A tended to present with more proteinuria, lower renal function, and more severe histopathologic injury than those with the AA genotype, although the time from the first urinary abnormality to the renal biopsy was no different between both groups. The logistic regression analysis indicated that even after adjusting for the effect of proteinuria and hypertension the GG genotype of NPHS1 G349A was an independent risk factor for the deteriorated renal function at the time of diagnosis. This study suggests that the NPHS1 G349A polymorphism may be associated with heavy proteinuria and a decline in renal function in patients with IgAN. (Lab Invest 2003, 83:1193-1200.

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Molecular Genetics in IgA Nephropathy

Cited by 27 publications

References 40 publications

Polymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System

Polymeric IgA1 from Patients with IgA Nephropathy Upregulates Transforming Growth Factor-β Synthesis and Signal Transduction in Human Mesangial Cells via the Renin-Angiotensin System

Interaction Between ACE and ADD1 Gene Polymorphisms in the Progression of IgA Nephropathy in Japanese Patients

Genetic Polymorphism of NPHS1 Modifies the Clinical Manifestations of Ig A Nephropathy

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